• 지질공학
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• 제19권3호
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• pp.295-306
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• 2009

본 연구는 지하수, 토양, 대기의 노출경로에 따라서 부산광역시 사상공단의 지하수와 토양이 인체와 환경에 미치는 영향을 평가하였다. 토양과 대기의 노출경로에 따른 발암 위해는 나타나지 않았으나, 지하수에서는 TCE와 PCE의 발암 위해성이 각각의 기준 한계값인 1.0E-6과 1.0E-5에 대해서 각각 6.7E-6과 1.0E-5로 나타나 발암 위해가 있는 것으로 판단되었다. 대기에서는 비발암성 위해가 나타나지 않았다. 토양의 위해계수와 위해지수는 각각 3.4E-5와 5E-5로서 기준 한계값(1.0) 보다 낮게 나타났으나, 지하수의 위해계수와 위해지수는 각각 0.7 (위해성이 없음)과 1.4(위해성이 있음)로 나타났다. TCE의 최소성분감소비(CRF)는 2.5로서 TCE의 정화작업이 요구된다. 18개의 노출인자에 대한 민감도 분석 결과, 8개의 노출 인자(비 발암 물질에 대한 평균 수명, 발암 물질에 대한 평균 수명, 체중, 노출기간, 노출빈도, 피부노출빈도, 토양 섭취율, 물 섭취율)의 변화에 따라서 위해도가 변화하는 것으로 나타났다.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.511-518
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• 2017

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by $SA-{\beta}-gal$ staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

• Toxicological Research
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• 제22권3호
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• pp.283-291
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• 2006

The survival and growth of epithelial cells depends on adhesion to the extracellular matrix. An adhesion signal may regulate the initiation of differentiation, since epidermal keratinocytes differentiate as they leave the basement membrane. A metabolically dead cornified cell envelope is the end point of epidermal differentiation so that this process may be viewed as a specialized form of programmed cell death. In order to investigate the precise cellular signaling events loading to terminal differentiation of keratinocytes, we have utilized HaCaT cells to monitor the biological consequences of $Ca^{2+}$ stimulation and numerous downstream signaling pathways, including activation of the extracellular signal-regulated protein kinase(ERK) pathway and activation of phosphatidylinositol 3-kinase(PI3K). The results presented in this study show that $Ca^{2+}$ function as potent agents for the differentiation of HaCaT keratinocytes, and this differentiation depends or the activation of ERK, Protein kinase B(PKB) and p70 ribosomal protein S6 kinase(p70S6K). Finally, the results show that the expression of Activator protein 1(AP-1; c-Jun and c-Fos) increased following $Ca^{2+}$-mediated differentiation of HaCaT cells, suggesting that ERK-mediated AP-1 expression is critical for initiating the terminal differentiation of keratinocytes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.495-499
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• 2014

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.339-344
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• 2004

Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권4호
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• pp.199-205
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• 2003

The p53 protein was discovered in 1979 as cellular 53-kD nuclear phosphoprotein bound to the large transforming antigen of SV40 virus. $P21^{WAF1/CIP1}$, which has been described as the critical downstream mediator of p53, is known to suppress DNA replication and arrest the G1 cell cycle by quaternary complex with cyclin D, cyclin-dependent kinase(CDK) and proliferating cell nuclear antigen(PCNA). In these days, some studies shows that the p21 can be induced by independent pathways. There are various reports about the expression of p21 (67%.82.4%) in oral squamous cell carcinoma. But these studies are mostly done in malignant tumor not in benign tumor. So we decided to study the expression of p21 in ameloblastoma and the relationship between p53 and p21 as a downstream mediator of p53 in ameloblastoma. We investigated the expression of p21 and p53 with the method of immunohistochemistry. We selected 30 cases of ameloblastoma tissue blocks (acanthomatous type: 5 cases, follicular type: 8 cases, plexiform type: 17 cases) imbedded in paraffin. We used 30 cases of normal gingival tissues and 30 cases of squamous cell carcinoma tissues (SCC) respectively and compared their results with those of ameloblastoma. We made slides with the streptavidin-biotin methods and used monoclonal antibody DO-7 (Novocastra, Newcastle, United Kingdom) as p53 antibody and monoclonal antibody M7202 (DAKO, California, U.S.A.) as p21 antibody. We used Pearson's correlation coefficient to analyse the relationship. The results were as follows: 1. p21 was expressed in ameloblastoma about 30% and this is lower than that of normal gingiva and SCC. 2. In normal gingiva and ameloblastoma, p21 expression was correlated with p53 expression. 3. In SCC, p21 were expressed about 83.3% and this is more than that of p53. But there was no correlation between p21 and p53 expression. We confirmed p21 expression and relation with p53 in ameloblastoma. But, to confirm the function of p21, more studies about p21 expression in malignant ameloblastoma and ameloblastic carcinoma are needed.

• 대한한방내과학회지
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• 제33권3호
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• pp.272-283
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• 2012

Objectives : The purpose of this study was to investigate the mechanism of protective effect of Jinmu-tang (JMT, Zhenwu-tang) extract on $H_2O_2$-induced cell death in C6 glial cells. Methods : Cultured C6 glial cells of white mice were pretreated with JMT extract and exposed to $H_2O_2$ for inducing cell death. We measure the cell viability by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and investigate the cell morphology using a light microscope after crystal violet (CV) staining. Reactive oxygen species (ROS) formation was analyzed using a flow cytometer and a fluorescent microscope after staining with 2'7'-dichlorofluorescein diacetate (DCF-DA). DNA fragmentation was analyzed using a flow cytometer after propidium iodide (PI) staining and nuclei morphology was investigated using a fluorescent microscope after 2-[4-amidinophenyl]-6-indo-lecarbamidine dihydrochloride (DAPI) staining. We analyzed expression of Bax, processing of procaspase-3 and poly (ADP-ribose) polymerase (PARP), and activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) by western blot method. Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) secretion was analyzed using Quantikine kit. Results : We determined the elevated cell viability by JMT extract on $H_2O_2$-induced C6 glial cell death. ROS formation, DNA fragmentation, $I{\kappa}B{\alpha}$ phosphorylation, NF-${\kappa}B$ activation, and secretion of TNF-${\alpha}$ induced by $H_2O_2$ are inhibited by JMT extract pre-treatment. JMT extract inhibits Bax expression, processing of caspase-3 and PARP that are critical biochemical markers of apoptotic cell death. Conclusions : These results suggest that JMT extract has a protective effect on $H_2O_2$-induced C6 glial cell death in various pathways.

• Journal of Plant Biotechnology
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• 제41권3호
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• pp.107-115
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• 2014

식물지방은 주로 종자에서 생산되는데 인류에게 필수 지방산을 공급하는 식품 뿐 아니라 바이오디젤 등 산업원료로 그 이용가치가 크다. 식물지방의 수요 증가에 따른 식물지방의 생산증대가 필요하다. 식물지방을 종자 이외의 바이오매스가 큰 식물의 잎에서 생산한다면 식물지방 생산 증진이 가능할 것이다. 잎은 지방을 생산하는 기관이 아니며 주로 광합성을 통해 탄소를 고정하여 다른 기관으로 탄소를 공급하는 기능을 하고 있어 지방을 생산 축적하는 기관으로 전환하는 데는 많은 고려가 필요하다. 그럼에도 불구하고 최근 지방합성 조절인자인 WRI 유전자, 지방을 생성하는 acyltransferase인 DGAT 유전자의 발현에 의해 잎에서 지방을 합성할 수 있었다. 또한 지방의 분해를 안정화하는 올레오신 단백질의 추가 도입으로 잎에서 건조중량당 15%의 중성지방 생산을 보여 잎에서 지방생산 가능성을 보여주었다(Vanhercke et al. 2014). 앞으로 바이오매스에서 지방을 생산하는 연구가 활발할 것으로 예측되며 이 기술을 식용작물이 아닌 비식용이며 바이오매스가 큰 거대억새 등에 도입하여 농지로 적합하지 않은 열악한 토지 및 간척지 등에 재배하여 실용화한다면 미래 지속 생산 가능 친환경 바이오 원료 생산 자원으로 사용 가능하리라 사료된다.

• 대한의생명과학회지
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• 제3권2호
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• pp.83-88
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• 1997

범발성 혈관내 응고증은 패혈증 환자들에 있어 빈번히 발생하며 여러 가지 위급한 질병 상태에 관계하는 병리학적 상황이다. 범발성 혈관내 응고증은 기존의 복잡한 임상 상황을 더욱 어렵게 만들어서 높은 사망률의 원인이 된다. 그럼에도 불구하고 그것의 병인적 기전들은 완전히 규명되지 않았다. 본 연구는 범발성 혈관내 응고증의 발생에 관여하는 병인적 기전들의 이해를 위해 전향적으로 계획되었다. 15마리의 쥐를 대상으로 해서 연구목적에 따라 세 군으로 나누었다：I 군은 대조군으로서 내독소를 투여하지 않은 쥐들이고 (n=5), II 군은 내독소 투여 후 12시간이 경과한 쥐들이며 (n=5), III군은 내독소 투여 후 24시간이 경과한 쥐들이었다 (n=5). 실험적 범발성 혈관내 응고증은 일정량의 내 독소를 한번에 투여하여 유도하였다 (1mg/kg, E. coli serotype 055:B5). 실험대상 쥐들의 심장으로부터 직접 채혈하여 혈소판수, 섬유소원 농도, plasminogen 농도, 항트롬빈 III 농도, D-dimer, 보체성분 (C3 및 C4)을 측정하였다. 내독소를 투여한 II 군과 III 군에 있어 혈소판수, 섬유소원 (III 군의 경우는 오히려 증가), plasminogen, 항트롬빈 III, 그리고 C3등의 혈중 농도들이 대체로 감소하였고 D-dimer 농도는 증가함으로써 명백한 범발성 혈관내 응고증이 관찰되었다. 본 연구 결과들은 내독소에 의해 응고계, 섬유소용해계, 그리고 보체계와 같은 여러경로의 활성화가 유도될 수 있으며, 이로해서 범발성 혈관내 응고증 및 이차적인 중복 장기기능 부전이 발생하리라는 점을 시사하고 있다. 결국, 이와같은 실험적인 내독소 유도 범발성 혈관내 응고증에 있어 응고계 및 섬유소 용해계의 활성을 일으키는 다양한 기전에 관한 축척된 지식들은 그와 같은 질병의 예방 혹은 치료방법을 제공해 줄 것이다.

• 방사성폐기물학회지
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• 제12권2호
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• pp.121-133
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• 2014

사용후핵연료를 포함하는 고준위 방사성폐기물을 지질학적 조건이 안정적인 지하 3~5 km의 심도에 처분할 수 있다면 다음과 같은 많은 장점이 있는 것으로 평가되고 있다. 즉, (1)암반 수리전도도가 매우 낮아 지하수가 생태계까지 도달하는데 속도가 현저히 감소되며, (2)상부층 두께로 인하여 생태계와의 이격거리 확보에 유리하고, (3)지하수가 환원상태이므로 핵종의 용해도가 매우 낮을 뿐만 아니라 (4)오랜 연령의 지하수에서는 핵종이 흡착된 콜로이드 생성과 이동이 극히 제한된다는 점이다. 이와 관련하여 심부시추공 처분(Deep Borehole Disposal) 연구는 심층 처분(Deep Geological Disposal) 시스템에 대한 이상적인 처분 대안기술로서 꾸준하게 진행되어 왔다. 본 논문에서는 최근 심부 시추기술이 비약적으로 발전됨에 따라 의미있게 연구가 진행되고 있는 심부시추공 처분시스템을 국내 적용하기 위한 초기 단계로서 해외의 심부시추공 처분시스템 기술개발 사례를 분석하였다. 이를 통하여 심부시추공 처분에 대한 일반적인 개념과 심부시추공 처분시스템 개념을 도출한 연구사례를 국가별로 정리하였다. 이들 분석결과는 향후 심부시추공 처분기술의 국내 적용을 위한 입력자료로서 유용하게 활용될 수 있을 것이다.